Because there vaccines for other viral diseases, varicella has emerged as the childhood exanthem with the highest risk of serious complications. As antiviral drugs and varicella vaccines are developed, decisions must be made about their administration to normal children, which requires a better understanding of varicella-zoster virus (VZV) replication and immunity in the normal host. A sensitive radioimmunoassay for VZV specific IgG,IgM and IgA antibodies will be used to analyze early humoral immunity in children with varicella. Although deficiencies of cellular immunity are associated with severe varicella, information about cellular immunity to VZV is limited. T-lymphocyte proliferation and T-lymphocyte cytotoxicity will be assessed in this study. Studies of other viral infections indicate that T-lymphocyte cytotoxicity is an important early immune response; this response has not been studied in children with varicella. Present concepts of resistance to viral infection suggest that host defenses which do not require immune recognition of the virus are important in the early restriction of viral replication. The production of interferons and activation of the interferon-induced enzyme 2-5A synthetase will be investigated as a non-specific host response to VZV. The analysis of immunity to specific VZV proteins following natural varicella is important for the evaluation of varicella vaccine-induced immunity and for the possible development of VZV sub-unit vaccines. VZV monoclonal antibodies will be used to purify VZV proteins for assays of humoral and cellular immunity to components of the virus. These methods will be used to analyze the responses of normal and immunocompromised children with varicella, VZV-immune subjects and varicella vaccine recipients. The skin infection with varicella suggests that viremia is important in the pathogenesis of primary VZV. New methods will be applied to the investigation of the role of virus infection of peripheral blood mononuclear cells in causing the symptoms of varicella. Finally, the possibility that laboratory tests can be used to predict the severity of varicella will be investigated. The identification of such laboratory markers for the likelihood of serious infection would be very helpful in decisions about the initiation of antiviral therapy.